Bi-directional communication between the nervous and immune systems occurs through neuroendocrine mechanisms and innervation of lymphoid tissue. Psychological or physical stressors that activate these pathways can alter immunity and disease resistance. However, the immunological consequences of "stress" in immunologically normal individuals has yet to be definitely and causally associated with an increased susceptibility to infection. This is not to say that psychological stress has never been reported to impair immunity in humans, but rather that when such a relationship has been reported (or suspected), the immune systems of subjects appear to have been altered, prior to stressor exposure, by aging, viremia, cancer, or an autoimmune, allergic, or inflammatory disease. Such observations suggest that the impact and clinical consequences of a psychosocial state or a stressor on the immune system will be more profound in pharmacologically immunosuppressed animals than in immunologically "normal" animals. Experiments to test this idea will use individually and group-housed BALB/c mice to establish distinct groups with different neuropsychological characteristics (psychological states). Animals in both housing conditions will be pharmacologically immunosuppressed with cyclophosphamide (CY) and then infected with herpes simplex virus type-1 (HSV-1). Any differences in the immune responses to the infection will be attributed to the neuropsychological state of the mice. Thus, to begin to examine the link between psychosocial factors and immune function in immunosuppressed animals, the experiments in this AREA application will satisfy two specific aims. AIM number 1 proposes to determine, in immunocompromised animals, whether a psychosocial state influences the immune response to HSV-1 infection. AIM number 2 proposed to determine, in immunocompromised animals, whether a psychosocial state influences the recovery of immune responsiveness to HSV-1.